The low dose-rate studies proposed address some basic issues in radiation biology, but their principle justification is their pragmatic usefulness in brachytherapy. Sophisticated after-loading devices used in interstitial brachytherapy are expensive to purchase and to maintain because they consist of many channels and a large inventory of radioactive sources which must be replaced several times each year. The new initiative in brachytherapy involves PULSED rather than CONTINUOUS low dose-rate irradiation. Only a single radioactive source is required, moving through the implant, with dwell times determined by the differential radioactive loading required. This allows improved optimization of dose, the need to replace only a single radioactive source, improved radiation safety and also avoids the variation of dose-rate between patients which is unavoidable with conventional Ir-192 implants. The radiobiological question is - what pulse length and pulse frequency is indistinguishable from continuous low dose-rate irradiation? Dose-rate data for cell lines of human origin relevant to brachytherapy (carcinoma of the cervix, melanoma, breast carcinoma, astrocytoma) will be analyzed to obtain a frequency distribution of values of a and b, the constants in the linear-quadratic dose response relationship and T(1/2), the half-time for repair of sub-lethal damage. Some low dose rate data sets are available from the literature, or from studies previously completed in this laboratory. However, these studies were not designed specifically for extraction of the parameters alpha, beta, and T(1/2), and so result in considerable imprecision in the estimated values of these parameters. Therefore it is proposed to obtain additional data for a range of cell lines, with emphasis on the dose-rate range from low dose rate to 10 cGy/min which is required to obtain a good estimate of the half-time of repair, and to distinguish possible fast and slow components of repair. To avoid mechanical breakdowns, the longer the interval between brachytherapy pulses the better; the radiobiological data will be used to determine the longest pulse interval and corresponding pulse length required to result in cell surviving fractions essentially equal to those produced by continuous low dose-rate irradiation at 60 cGy/hour will be estimated. Radiobiological experiments will then be performed to test this equivalence of pulsed and continuous irradiation using iridium 192 sources and representative cell lines.